Project 3 Project Abstract The work described in this project aims to expedite the process from drug discovery to clinical application by identifying patients who are likely to respond to a particular drug, or drug combination, before it is administered to them. It describes a plan that takes advantage of new methods to culture human cells, maintaining their innate physiologic properties and making them amenable to screening for drug responses. The project uses cells from cystic fibrosis patients carrying a variety of disease-causing mutations and determines which patients, and which mutations, respond to various drugs. In cases where multiple drugs elicit responses, the ability of the drugs to act additively or even synergistically will be tested. These studies will serve as pre- clinical assessments for later clinical trials. This study focuses on cystic fibrosis, but as small molecule screens identify putative drugs for other disorders, the approach outlined here would be applicable to any disorder in which a screening process could be developed.